Thermal behavior and decomposition kinetics of rifampicin polymorphs under isothermal and non-isothermal conditions

The thermal behavior of two polymorphic forms of rifampicin was studied by DSC and TG/DTG. The thermoanalytical results clearly showed the differences between the two crystalline forms. Polymorph I was the most thermally stable form, the DSC curve showed no fusion for this species and the thermal decomposition process occurred around 245 ºC. The DSC curve of polymorph II showed two consecutive events, an endothermic event (Tpeak = 193.9 ºC) and one exothermic event (Tpeak = 209.4 ºC), due to a melting process followed by recrystallization, which was attributed to the conversion of form II to form I. Isothermal and non-isothermal thermogravimetric methods were used to determine the kinetic parameters of the thermal decomposition process. For non-isothermal experiments, the activation energy (Ea) was derived from the plot of Log β vs 1/T, yielding values for polymorph form I and II of 154 and 123 kJ mol-1, respectively. In the isothermal experiments, the Ea was obtained from the plot of lnt vs 1/T at a constant conversion level. The mean values found for form I and form II were 137 and 144 kJ mol-1, respectively.

Utilização dos subprodutos da fresagem do osso subcondral em substituição ao enxerto autólogo esponjoso em artrodeses de carpo de cães

A artrodese rádio-cárpica é procedimento radical usado no tratamento de fraturas e luxações do carpo, com danos à fibrocartilagem palmar e às estruturas ligamentares de sustentação, decorrentes de hiperextensão. Para este estudo foram selecionados 15 cães, submetidos à artrodese rádio-cárpica, entre abril/02 e julho/04. Foram estudados os casos quanto à formação de calo ósseo e às complicações pós-cirúrgicas. A técnica consistiu na ostectomia da superfície articular do rádio, expondo-a e retificando-a. Os subprodutos desta fresagem foram reintroduzidos como enxerto após sua redução em tamanho com rugina. Para a estabilização articular, em todos os casos, foram usadas placas compressivas. Foram realizados exames radiográficos imediatamente à intervenção cirúrgica e em intervalos de 30 dias, até a total fusão articular. Os resultados obtidos neste estudo, com fusão da articulação em até 300 dias de pós-cirúrgico em 80% dos casos estudados, foram semelhantes aos dispostos para as técnicas que utilizam enxertos autólogos esponjosos, sendo que, em 68% dos pacientes, a recuperação se deu sem qualquer complicação significativa. Pequenas complicações, como o aumento de volume, foram observadas em 22% dos casos, não determinando qualquer alteração no resultado final. Tais resultados viabilizam a técnica descrita, demonstrando a exeqüibilidade da utilização dos subprodutos da fresagem do osso subcondral como enxerto em artrodeses de carpo em cães.

Multifractality in plasma edge electrostatic turbulence

Plasma edge turbulence in Tokamak Chauffage Alfven Bresilien (TCABR) [R. M. O. Galvao et al., Plasma Phys. Contr. Fusion 43, 1181 (2001)] is investigated for multifractal properties of the fluctuating floating electrostatic potential measured by Langmuir probes. The multifractality in this signal is characterized by the full multifractal spectra determined by applying the wavelet transform modulus maxima. In this work, the dependence of the multifractal spectrum with the radial position is presented. The multifractality degree inside the plasma increases with the radial position reaching a maximum near the plasma edge and becoming almost constant in the scrape-off layer. Comparisons between these results with those obtained for random test time series with the same Hurst exponents and data length statistically confirm the reported multifractal behavior. Moreover, the persistence of these signals, characterized by their Hurst exponent, present radial profile similar to the deterministic component estimated from analysis based on dynamical recurrences. (C) 2008 American Institute of Physics.

Identification of possible targets of the Aspergillus fumigatus CRZ1 homologue, CrzA

Background: Calcineurin, a serine/threonine-specific protein phosphatase, plays an important role in the control of cell morphology and virulence in fungi. Calcineurin regulates localization and activity of a transcription factor called CRZ1. Recently, we characterize Aspergillus fumigatus CRZ1 homologue, AfCrzA. Here, we investigate which pathways are influenced by A. fumigatus AfCrzA during a short pulse of calcium by comparatively determining the transcriptional profile of A. fumigatus wild type and.AfcrzA mutant strains. Results: We were able to observe 3,622 genes modulated in at least one timepoint in the mutant when compared to the wild type strain (3,211 and 411 at 10 and 30 minutes, respectively). Decreased mRNA abundance in the Delta crzA was seen for genes encoding calcium transporters, transcription factors and genes that could be directly or indirectly involved in calcium metabolism. Increased mRNA accumulation was observed for some genes encoding proteins involved in stress response. AfCrzA overexpression in A. fumigatus increases the expression of several of these genes. The deleted strain of one of these genes, AfRcnA, belonging to a class of endogenous calcineurin regulators, calcipressins, had more calcineurin activity after exposure to calcium and was less sensitive to menadione 30 mu M, hydrogen peroxide 2.5 mM, EGTA 25 mM, and MnCl(2) 25 mM. We constructed deletion, overexpression, and GFP fusion protein for the closely related A. nidulans AnRcnA. GFP

Therapeutic Efficacy of Cintredekin Besudotox (IL13-PE38QQR) in Murine Lung Fibrosis Is Unaffected by Immunity to Pseudomonas aeruginosa Exotoxin A

Background: We have previously explored a therapeutic strategy for specifically targeting the profibrotic activity of IL-13 during experimental pulmonary fibrosis using a fusion protein comprised of human IL-13 and a mutated form of Pseudomonas aeruginosa exotoxin A (IL13-PE) and observed that the intranasal delivery of IL13-PE reduced bleomycin-induced pulmonary fibrosis through its elimination of IL-13-responsive cells in the lung. The aim of the present study was to determine whether the presence of an immune response to P. aeruginosa and/or its exotoxin A (PE) would diminish the anti-fibrotic properties of IL13-PE. Methodology/Principal Findings: Fourteen days after P. aeruginosa infection, C57BL/6 mice were injected with bleomycin via the intratracheal route. Other groups of mice received 4 doses of saline or IL13-PE by either intranasal or intraperitoneal application, and were challenged i.t. with bleomycin 28 days later. At day 21 after bleomycin, all mice received either saline vehicle or IL13-PE by the intranasal route and histopatological analyses of whole lung samples were performed at day 28 after bleomycin. Intrapulmonary P. aeruginosa infection promoted a neutralizing IgG2A and IgA antibody response in BALF and serum. Surprisingly, histological analysis showed that a prior P. aeruginosa infection attenuated the development of bleomycin-induced pulmonary fibrosis, which was modestly further attenuated by the intranasal administration of IL13-PE. Although prior intranasal administration of IL13-PE failed to elicit an antibody response, the systemic administration of IL13-PE induced a strong neutralizing antibody response. However, the prior systemic sensitization of mice with IL13-PE did not inhibit the anti-fibrotic effect of IL13-PE in fibrotic mice. Conclusions: Thus, IL13-PE therapy in pulmonary fibrosis works regardless of the presence of a humoral immune response to Pseudomonas exotoxin A. Interestingly, a prior infection with P. aeruginosa markedly attenuated the pulmonary fibrotic response suggesting that the immune elicitation by this pathogen exerts anti-fibrotic effects.

Evaluation of Primary Resistance to HIV Entry Inhibitors Among Brazilian Patients Failing Reverse Transcriptase/Protease Inhibitors Treatment Reveal High Prevalence of Maraviroc Resistance-Related Mutations

Entry inhibitor is a new class of drugs that target the viral envelope protein. This region is variable; hence resistance to these drugs may be present before treatment. The aim of this study was to analyze the frequency of patients failing treatment with transcriptase reverse and protease inhibitors that would respond to the entry inhibitors Enfuvirtide, Maraviroc, and BMS-806. The study included 100 HIV-1 positive patients from one outpatient clinic in the city of Sao Paulo, for whom a genotype test was requested due to treatment failure. Proviral DNA was amplified and sequenced for regions of gp120 and gp41. A total of 80 could be sequenced and from those, 73 (91.3%), 5 (6.3%) and 2 (2.5%) were classified as subtype B, F, and recombinants (B/F and B/C), respectively. CXCR4 co-receptor use was predicted in 30% of the strains. Primary resistance to Enfuvirtide was found in 1.3%, following the AIDS Society consensus list, and 10% would be considered resistant if a broader criterion was used. Resistance to BMS-806 was higher; 6 (7.5%), and was associated to non-B strains. Strikingly, 27.5% of samples harbored one or more mutation among A316T, I323V, and S405A, which have been related to decreased susceptibility of Maraviroc; 15% of them among viruses predictive to be R5. A more common mutation was A316T, which was associated to the Brazilian B strain harboring the GWGR motif at the tip of V3 loop and their derivative sequences. These results may be impact guidelines for genotype testing and treatment in Brazil.

rst Transcriptional Activity Influences kirre mRNA Concentration in the Drosophila Pupal Retina during the Final Steps of Ommatidial Patterning

Background: Drosophila retinal architecture is laid down between 24-48 hours after puparium formation, when some of the still uncommitted interommatidial cells (IOCs) are recruited to become secondary and tertiary pigment cells while the remaining ones undergo apoptosis. This choice between survival and death requires the product of the roughest (rst) gene, an immunoglobulin superfamily transmembrane glycoprotein involved in a wide range of developmental processes. Both temporal misexpression of Rst and truncation of the protein intracytoplasmic domain, lead to severe defects in which IOCs either remain mostly undifferentiated and die late and erratically or, instead, differentiate into extra pigment cells. Intriguingly, mutants not expressing wild type protein often have normal or very mild rough eyes. Methodology/Principal Findings: By using quantitative real time PCR to examine rst transcriptional dynamics in the pupal retina, both in wild type and mutant alleles we showed that tightly regulated temporal changes in rst transcriptional rate underlie its proper function during the final steps of eye patterning. Furthermore we demonstrated that the unexpected wild type eye phenotype of mutants with low or no rst expression correlates with an upregulation in the mRNA levels of the rst paralogue kin-of-irre (kirre), which seems able to substitute for rst function in this process, similarly to their role in myoblast fusion. This compensatory upregulation of kirre mRNA levels could be directly induced in wild type pupa upon RNAi-mediated silencing of rst, indicating that expression of both genes is also coordinately regulated in physiological conditions. Conclusions/Significance: These findings suggest a general mechanism by which rst and kirre expression could be fine tuned to optimize their redundant roles during development and provide a clearer picture of how the specification of survival and apoptotic fates by differential cell adhesion during the final steps of retinal morphogenesis in insects are controlled at the transcriptional level.

Nd:YAG Laser Improves Biocompatibility of Human Dental Root Surfaces

Objective: Our goal was to compare the in vivo biocompatibility of dental root surfaces submitted to four different treatments after tooth avulsion followed by implantation into rat subcutaneous tissue. Background Data: Dental root surface preparation prior to replanting teeth remains a challenge for endodontists. Root surface changes made by Nd:YAG irradiation could be an alternative preparation. Methods: Forty-eight freshly extracted human dental roots were randomly divided into four treatment groups prior to implantation into rat subcutaneous tissue: G1, dry root, left in the environment up to 3 h; G2, the same treatment as G1, followed by a soaking treatment in a 2.4% sodium fluoride solution (pH 5.5); G3, root soaked in physiologic saline after avulsion for 72 h; G4, the same treatment as G1, followed by Nd:YAG laser irradiation (2.0 W, 20 Hz, 100 mJ, and 124.34 J/cm(2)). The animals were sacrificed 1, 7, and 45 d later. Histological and scanning electron microscopy analyses were done. Results: All dental roots were involved and in intimate contact with connective tissue capsules of variable thicknesses. Differences were observed in the degree of inflammation and in connective tissue maturation. In G3 the inflammatory infiltrate was maintained for 45 d, whereas the Nd:YAG laser irradiation (G4) led to milder responses. The overall aspects of the root surfaces were similar, except by the irradiated roots, where fusion and resolidification of the root surface covering the dentinal tubules were observed. Conclusion: Nd:YAG laser irradiation improves the biocompatibility of dental root and thus could be an alternative treatment of dental root prior to replantation.

Morphologic changes and removal of debris on apical dentin surfaces after Nd : YAG laser and diode laser irradiation

Objective: To verify the effects of laser energy on intracanal dentin surfaces, by analyzing the morphologic changes and removal of debris in the apical third of 30 extracted human teeth, prepared and irradiated with the Nd:YAG laser and diode laser. Background Data: Lasers have been widely used in endodontics. The morphologic changes in dentin walls caused by Nd: YAG and diode laser irradiation could improve apical seals and cleanliness. Materials and Methods: The protocol used for Nd: YAG laser irradiation was 1.5 W, 100 mJ, and 15 Hz, in pulsed mode, and for diode laser was 2.5 W in continuous mode. Each specimen was irradiated four times at a speed of 2 mm/sec with a 20-sec interval between applications. Five calibrated examiners scored the morphologic changes and debris removal on a 4-point scale. Results: In analyzing the scores, there were no statistically significant differences between the two types of laser for either parameter, according to Kruskal-Wallis testing at p = 0.05. The SEM images showed fusion and resolidification of the dentin surface, with partial removal of debris on the specimens irradiated with the Nd: YAG laser and the diode laser, compared with controls. Conclusion: Both lasers promote morphologic changes and debris removal. These alterations of the dentin surface appeared to be more evident in the Nd: YAG laser group, but the diode laser group showed more uniform changes.

Ultra-Structural Changes at the Apical Stop Irradiated with CO(2) Laser

Objective: This study evaluated ultra-structural dentine changes at the apical stop after CO(2) laser irradiation used during biomechanical preparation. Background: Most studies evaluating the sealing efficiency of CO(2) lasers have been carried out after apical root canal resections and retro-filling procedures. Methods: Sixty human canines were prepared with #1 to #6 Largo burs. The apical stops were established at 1 mm (n = 30) and 2 mm (n = 30) from the apex. Final irrigation was performed with 1% NaOCl and 15% EDTA followed by 20 ml of distilled and deionized water. Specimens were subdivided into three subgroups (n = 10 for each stop distance): GI-no radiation (n = 20); GII-3W potency (n = 20), GIII-5W potency (n = 20). After preparation, specimens were evaluated by scanning electron microscopy, with ultra-structural changes classified according to a scoring system based on six qualitatively different outcomes. Results: Statistical analysis using the Mann-Whitney test confirmed more intense results for the specimens irradiated at 5 W potency than at 3 W (p<0.0001). The Kruskal-Wallis test indicated that when using the same potencies (3 or 5 W) at 1 and 2 mm from the apex, there were no statistically significant differences in ultra-structural changes. Conclusions: Our results showed that ultra-structural changes ranged from smear layer removal to dentine fusion. As laser potency was increased from 3 to 5 W, ultra-structural changes included extensive fused lava-like areas sealing the apical foramen.